Preservation of personal care compositions

ABSTRACT

Formulations comprised of pyrone and a mixture of at least one cationic surfactant, such as for preservation of personal care compositions, are disclosed. Articles comprising the formulations are further disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority to U.S. ProvisionalPatent Application No. 62/640,105 filed Mar. 8, 2018, entitled“PRESERVATION OF PERSONAL CARE COMPOSITIONS”, the contents of which areincorporated herein by reference in their entirety.

FIELD OF INVENTION

The present invention is in the field of preservation of personal careformulations.

BACKGROUND OF THE INVENTION

Antimicrobial compositions are used, for example, in the health careindustry, food service industry, meat processing industry, and in theprivate sector by individual consumers.

Preservation of personal care products from microbial contamination hasbecome a difficult task since the available approved antimicrobials arevery few and those which have good antimicrobial activity are quitetoxic. Consumers seek for products for topical applications being freefrom toxic antimicrobials that can be used as preservatives.

Infection is a constant risk to any healthy person, and poses even ahigher risk to hospitalized patients. The risk of infection is furtherincreased when the natural infection barriers of skin or otherepithelial surfaces are breached during a surgical procedure, and/orotherwise in cases where bacteria normally present on the skin or in theair are allowed to access the interior surfaces of the body.

Hospital-acquired (nosocomial) infections occur even when good hygieneand sterile technique is followed, although the incidence is reduced.Despite even the most rigorous aseptic procedures, people cannot becompletely isolated from infectious agents.

The widespread use of antibacterial compositions indicates theimportance consumers place on controlling bacteria and othermicroorganism populations on skin. It is important, however, thatantibacterial compositions provide a substantial and broad-spectrumreduction in microorganism populations quickly and without problemsassociated with toxicity and skin irritation. In particular,antibacterial cleansing compositions typically contain an activeantibacterial agent, a surfactant, and various other ingredients, forexample, dyes, fragrances, pH adjusters, thickeners, and the like, in anaqueous carrier.

Despite being successful in controlling or eliminating bacterialinfections, widespread use of antibiotics both in human medicine and asa feed supplement in poultry and livestock production has led to drugresistance in many pathogenic bacteria. The evolution and spread ofresistance genetic determinants, multidrug resistant (MDR) bacteria thatcause life-threatening infections have been increasingly emerged, and assuch, the effectiveness of antibiotics has greatly diminished in thelast decade. Furthermore, as resistance spreads among bacteria, there isgreat concern that antibiotics treatment will become increasingly lesseffective and, in some cases, completely ineffective.

Nosocomial infections caused by antibiotic-resistant bacteria result inpatient suffer and mortality and impose a substantial burden on themedical system due to extended periods of hospitalization. The economicimpact of managing infections caused by nosocomial infections issubstantial, and costs are estimated to be more than $4 billionannually.

Currently, a number of blends are available for preservation of personalcare products where synergy between antimicrobials is exploited inlowering the concentration of individual ingredient. Another greatadvantage is that the microbes cannot develop resistance very easily ifthey are attacked by a combination of antimicrobials.

SUMMARY OF THE INVENTION

According to one aspect, the present invention provides a compositioncomprising a pyrone and at least one cationic surfactant in a ratio ofat least 70:30 by weight, respectively.

In some embodiments, the ratio of pyrone/cationic surfactant ranges from85:15 to 99:1 by weight, respectively.

In some embodiments, the pyrone is selected from the group consisting ofmaltol, ethyl maltol or any derivative thereof.

In some embodiments, the at least one cationic surfactant is a tertiaryammonium compound.

In some embodiments, the at least one cationic surfactant is aquaternary ammonium compound.

In some embodiments, the at least one cationic surfactant is a mixtureof at least one tertiary ammonium compound and at least one quaternaryammonium compound.

In some embodiments, the at least one cationic surfactant is a mixtureof at least two quaternary ammonium compounds.

In some embodiments, the at least one quaternary ammonium compound is amonomeric compound.

In some embodiments, the at least one quaternary ammonium compound is apolymeric compound.

In some embodiments, the ratio between the quaternary ammonium compoundsranges from 10:1 to 1:10.

According to another aspect, there is provided a composition comprisingmaltol and at least two cationic surfactants.

In some embodiments, the quaternary ammonium is selected from the groupconsisting of: benzyldimethyldodecylammonium chloride,didecyldimethylammonium chloride, dodecyltrimethylammonium chloride,hexadecyltrimethylammonium chloride, Polyquaternium-2,Polyquaternium-80, Polyquaternium-11, Polyquaternium-52,Polyquaternium-17, Sodium Cocamidopropyl PG-Dimonium Chloride Phosphate(Cola Lipid C), Laurdimoniumhydroxypropyl decylglucoside chloride(SugaQuat L-1010), Berberine, Berberrubine, Berberis vulgaris rootextract, Isopropylbenzyl butylnorberberine iodide, Palmatine,Jatrorrhizine, Coptisine, Ungeremine, Epiberberine, Pseudoberberine,Stepharanine, Sinapine, or any combination thereof.

In some embodiments, the formulation is an antimicrobial formulation.

In some embodiments, the formulation is for use in the treatment of amedical, cosmetic and/or cosmeceutical condition.

In some embodiments, the formulation further comprises a chelatingagent, or a salt thereof.

In some embodiments, the formulation further comprises 0.1% to 10% (w/w)of the chelating agent, or a salt thereof.

In some embodiments, the chelating agent is selected from the groupconsisting of: Disodium EDTA—Ethylenediaminetetraacetic acid disodiumsalt, EDTMP—Ethylenediamine tetra (methylene phosphonic acid), Alaninedi-acetic acid, Ascorbic acid, Sodium Gluconate, Zinc gluconate,Vanillin, Ethylenediamine-N,N-discuccinic acid trisodium salt(Natrlquest E30), pentetic acid (DTPA), and any combination thereof.

According to another aspect, there is provided an article comprising thedisclosed formulation in any embodiment thereof.

In some embodiments, the article is a personal care product.

In some embodiments, the article is selected from the group consistingof: a fabric, a bandage, a wipe, a pledget, a swab, a suppository, adressing, a solution, a mousse, a pad, and a patch.

In some embodiments, the product comprises a formulation in the formselected from the group consisting of: paste, cream, lotion, foam, gel,emulsion, an ointment, and soap.

In some embodiments, the article is for use in the treatment of acondition selected from medical, cosmetic and cosmeceutical condition.

According to another aspect, there is provided a method of inhibiting orreducing the formation of load of a microorganism in and/or on anarticle, the method comprising contacting the article with the disclosedformulation in an embodiment thereof.

In some embodiments, the microorganism is selected from bacteria, moldsand fungi.

In some embodiments, the bacteria are Gram-positive bacteria selectedfrom the group consisting of: Staphylococcus aureus, Staphylococcusepidermidis, and Bacillus cereus; or Gram-negative bacteria selectedfrom the group consisting of: Escherichia coli and Pseudomonasaeuruginosa.

In some embodiments, the fungi are Candida albicans.

In some embodiments, the mold is Aspergillus niger.

According to another aspect, there is provided a method of preserving acosmetic product, comprising adding to the cosmetic product thedisclosed formulation in an embodiment thereof.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 Presents a graph showing the effect of different chelators in aformulation on stainless steel 316; and

FIG. 2 presents a graph showing the effect of a formulation withdisodium EDTA on stainless steel 304.

DETAILED DESCRIPTION OF THE INVENTION

The present invention, in some embodiments thereof, relates tocompositions and, more particularly, but not exclusively, to personalcare compositions exhibiting antimicrobial (also referred to as“anti-micro-organic”) activity, articles containing same, and usesthereof in, for example, reducing or preventing growth ofmicroorganisms.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details set forth in the following description orexemplified by the Examples. The invention is capable of otherembodiments or of being practiced or carried out in various ways.

High quality antimicrobial compositions are desirable as they provide agood solution to biofouling and/or infection processes and/or formationof biofilms on a surface. Conventional personal care compositionspresent several drawbacks, as many of these compositions are referred toas being toxic (or releasing toxic materials to the environment),instable, inefficient or are limited in preventing (or completediminishing) microorganism growth, expensive and produced viacomplicated manufacturing processes which at times require expensiveequipment for their manufacture.

Herein throughout, by “composition” it is further meant to refer to aformulation.

The present inventors have designed non-toxic antimicrobial formulations(also referred to as “blends”).

According some embodiments of the present invention, there is provided acomposition comprising a compound comprising a pyrone and at least onecationic surfactant.

In some embodiments, the pyrone is maltol.

In some embodiments, the pyrone is a maltol derivative whereinderivative refer to a pyrone having at least 80% antimicrobial activitysimilar to maltol combined with the at least one cationic surfactant, asdisclosed herein.

In some embodiments, the cationic surfactant is a naturalproduct-derived cationic surfactant.

In some embodiments, the cationic surfactant is quaternary ammonium.

In some embodiments, the cationic surfactant is a naturalproduct-derived quaternary ammonium.

In some embodiments, a formulation as described herein is a 100% naturalproduct-derived antimicrobial formulation.

In some embodiments, the quaternary ammonium is selected from, withoutbeing limited thereto, benzyldimethyldodecylammonium chloride,didecyldimethylammonium chloride, dodecyltrimethylammonium chloride,hexadecyltrimethylammonium chloride, Polyquaternium-2,Polyquaternium-80, Polyquaternium-11, Polyquaternium-52,Polyquaternium-17, Sodium Cocamidopropyl PG-Dimonium Chloride Phosphate(Cola Lipid C), Laurdimoniumhydroxypropyl decylglucoside chloride(SugaQuat L-1010), Berberine, Berberrubine, Berberis vulgaris rootextract, Isopropylbenzyl butylnorberberine iodide, Palmatine,Jatrorrhizine, Coptisine, Ungeremine, Epiberberine, Pseudoberberine,Stepharanine, Sinapine, and any combination thereof.

In some embodiments, maltol and a quaternary ammonium are present at aratio that ranges from 70:30 to 99:1, by weight, respectively. In someembodiments, maltol and a quaternary ammonium are present at a ratiothat ranges from 70:30 to 99:1, 80:20 to 99:1, 80:20 to 90:10, 80:20 to98:2, or 80:20 to 95:5, by weight, respectively, including any rangetherebetween.

As demonstrated in the Examples section that follows, the presentinventors have shown that compositions (e.g., formulations) comprising apyrone and a cationic surfactant, being at certain predetermined ratios,exhibit a desired stability as well as improved antimicrobialactivities, compared to other compositions comprising differentmaterials from the invented formulations or from formulations comprisingthe same materials but having different volume or weight ratios thereof.

As demonstrated in the Examples section that follows, the presentinventors have shown that a specific ratio of the above-mentionedcompounds impart the formulation with antimicrobial activities.

The present inventors have also shown that the disclosed formulation canbe used to impart to articles the antimicrobial activities.

According some embodiments of the present invention there is provided acomposition comprising maltol, and at least one cationic surfactant orsalt thereof.

In some embodiments, the cationic surfactant and maltol are present at aratio that ranges from 15:85 to 2:98, by weight, respectively.

According some embodiments of the present invention there is provided acomposition comprising maltol, a first cationic surfactant and a secondcationic surfactant.

In some embodiments, the first cationic surfactant is a quaternaryammonium. In some embodiments, the second cationic surfactant is aquaternary ammonium.

In some embodiments, a first cationic surfactant, a second cationicsurfactant and maltol are present at a ratio of 2.5:2.5:95 to 5:5:90 byweight, respectively.

In some embodiments, a first cationic surfactant, a second cationicsurfactant and maltol are present at a ratio of 1:1:95 to 5:5:90, 2:2:96to 5:5:90, 2.3:2.3:95.4 to 5:5:90, 3:3:94 to 5:5:90, or 4:4:92 to5:5:90, by weight, respectively, including any range therebetween.

In some embodiments, the formulation further comprises a chelatingagent, or a salt thereof.

In some embodiments, the formulation further comprises 0.1% to 10% (w/w)of a chelating agent, or a salt thereof. In some embodiments, theformulation further comprises 0.1% to 9% (w/w), 0.1% to 8% (w/w), 0.1%to 7% (w/w), 0.1% to 6% (w/w), 0.1% to 5% (w/w), 0.2% to 10% (w/w), 0.3%to 10% (w/w), 0.5% to 10% (w/w), 1% to 10% (w/w), 0.2% to 7% (w/w), 0.3%to 7% (w/w), 0.5% to 7% (w/w), 1% to 7% (w/w), 0.2% to 5% (w/w), 0.3% to5% (w/w), 0.5% to 5% (w/w), or 1% to 5% (w/w), of a chelating agent, ora salt thereof, including any range therebetween.

In some embodiments, the chelating agent is selected from the groupconsisting of: Disodium EDTA—Ethylenediaminetetraacetic acid disodiumsalt, EDTMP—Ethylenediamine tetra (methylene phosphonic acid), Alaninedi-acetic acid, Ascorbic acid, Sodium Gluconate, Zinc gluconate,Vanillin, Sodium vanillate, Ethylenediamine-N,N-discuccinic acidtrisodium salt (Natrlquest E30), pentetic acid (DTPA), and anycombination thereof.

As used herein, the term “chelating agent” refers to any organic orinorganic compound that will bind to a metal ion having a valencegreater than one. “Chelating agents” include, but are not limited to,organic chelating agents or any other chelating agent that will chelatedivalent ions such as Ca²⁺, Mg²⁺, Mn²⁺, Fe²⁺, and Zn²⁺.

In some embodiments, a formulation according to the present inventioncomprising a chelating agent, or a salt thereof, has a superiorstability than the corresponding formulation without a chelating agent,or a salt thereof.

In some embodiments, a formulation according to the present inventioncomprising a chelating agent, or a salt thereof, has a longer shelf livethan the corresponding formulation without a chelating agent, or a saltthereof.

In some embodiments, a formulation according to the present inventioncomprising a chelating agent, or a salt thereof, preserves its colorduring manufacturing processes of a personal care product, as comparedto the corresponding formulation without a chelating agent, or a saltthereof.

In some embodiments, the chelating agent, or a salt thereof may be usedin an amount that is effective to bind the aforementioned metals(hereinafter alternatively referred to as an “effective amount”),typically an amount ranging from about 0.01% to about 10 weight % of thecomposition.

In some embodiments the cationic surfactant is a tertiary ammoniumcation.

In some embodiments the tertiary ammonium cation is other than EthylLauroyl Arginate. In some embodiments the tertiary ammonium cation isother than formula (1) from patent application US20100028325A1.

In some embodiments, the cationic surfactant is a quaternary ammoniumcation (also referred to as: “quat”).

In some embodiments, the quaternary ammonium cation is positivelycharged polyatomic ion of the structure NR₄ ⁺. In some embodiments, R isan alkyl group. In some embodiments, R is an aryl group. In someembodiments, the quaternary ammonium cation is derived from a quaternaryammonium salt. In some embodiments, the quaternary ammonium salt (e.g.,benzyldimethyldodecylammonium, didecyldimethylammonium) comprises acounteranion.

In some embodiments, the quaternary ammonium cation and maltol arepresent at a ratio of at least 50:50 by weight, respectively.

As used herein, the term “alkyl” describes an aliphatic hydrocarbonincluding straight chain and branched chain groups. Preferably, thealkyl group has 21 to 100 carbon atoms, and more preferably 21-50 carbonatoms. Whenever a numerical range; e.g., “21-100”, is stated herein, itimplies that the group, in this case the alkyl group, may contain 21carbon atoms, 22 carbon atoms, 23 carbon atoms, etc., up to andincluding 100 carbon atoms. In the context of the present invention, a“long alkyl” is an alkyl having at least 20 carbon atoms in its mainchain (the longest path of continuous covalently attached atoms). Ashort alkyl therefore has 20 or less main-chain carbons. The alkyl canbe substituted or unsubstituted, as defined herein

The term “alkyl”, as used herein, also encompasses saturated orunsaturated hydrocarbon, hence this term further encompasses alkenyl andalkynyl.

The term “alkenyl” describes an unsaturated alkyl, as defined herein,having at least two carbon atoms and at least one carbon-carbon doublebond. The alkenyl may be substituted or unsubstituted by one or moresubstituents, as described hereinabove.

The term “alkynyl”, as defined herein, is an unsaturated alkyl having atleast two carbon atoms and at least one carbon-carbon triple bond. Thealkynyl may be substituted or unsubstituted by one or more substituents,as described hereinabove.

The term “cycloalkyl” describes an all-carbon monocyclic or fused ring(i.e. rings which share an adjacent pair of carbon atoms) group whereone or more of the rings does not have a completely conjugatedpi-electron system. The cycloalkyl group may be substituted orunsubstituted, as indicated herein.

The term “aryl” describes an all-carbon monocyclic or fused-ringpolycyclic (i.e. rings which share adjacent pairs of carbon atoms)groups having a completely conjugated pi-electron system. The aryl groupmay be substituted or unsubstituted, as indicated herein.

In some embodiments, the counteranion is halide. In some embodiments,the halide is chloride. In some embodiments, the halide is bromide.

In some embodiments, the counteranion is sulfonate. In some embodimentsthe sulfonate is mesylate.

In some embodiments, the formulation is a preservative e.g., for apersonal care composition.

The formulation of the cationic surfactant is an emulsifier.

As used herein and in the art, the term “emulsifier” is intended to meana surface-active agent that facilitates the mixing of two or more liquidsubstances that would separate into its component parts under normalconditions.

In some embodiments, the cationic surfactant provides detersivefunctionality to a formulation or act simply as wetting agents.

In some embodiments, the formulation is devoid of paraben. In someembodiments, the formulation is devoid of formaldehyde. In someembodiments, the formulation is devoid of formaldehyde and is furtherdevoid of paraben.

In some embodiments, the formulation is not pH dependent.

In some embodiments of the present invention, the formulation furthercomprises a buffer solution or a pH adjuster to control the desired pHof the formulation.

As used herein, the terms “formulation”, or “blend”, which are usedherein throughout interchangeably, refer to a vehicle composition in theform of emulsion, lotion, cream, gel etc., that optionally furthercomprises physiologically acceptable carriers and/or excipients andoptionally other chemical components such as cosmetically,cosmeceutically or pharmaceutically active agents (e.g., drugs). Theformulation can optionally further comprise a carrier, and optionallyadditional active agents and/or additives e.g., anti-freezing agents).

In some embodiments, the term “by weight” means by weight of the totalcomposition.

As used herein, the term “physiologically acceptable” means approved bya regulatory agency of the Federal or a state government or listed inthe U.S. Pharmacopeia or other generally recognized pharmacopeia for usein animals, and more particularly in humans.

Herein the term “excipient” refers to an inert substance added to aformulation as described herein to further facilitate processes andadministration of the active ingredients.

The formulation of the invention can be prepared by any commonly usedmethod for preparing a composition of materials. For example, thecomponents of the formulations may be added and mixed together, or oneof the components may be added to the other in the form of a solutionwhich may, if desired, be evaporated or lyophilized after mixing forobtaining a homogeneous and stable solution or suspension.

In some embodiments, the disclosed composition, in any embodimentthereof, is a stable formulation.

As used herein the terms “stable formulation”, or “long-lastingformulation”, mean that the formulation remains in a state or conditionof sufficient stability to have utility as a personal care agent, whilemaintaining the antimicrobial activity (with ±20% variation). Forexample, and without limitation, the formulation has a sufficientstability to allow storage at a convenient temperature, e.g., between10° C. and 30° C., for a reasonable period of time of e.g., longer thanone month, longer than three months, longer than six months, and longerthan one year.

In some embodiments, the disclosed composition is incorporated intosubstrates susceptible to microbial growth as a preservative or apersonal care system. For example, the preservative system may beincorporated into or be a personal care product, such as a shampoo,conditioner, cream, lotion, cosmetic, or soap; a household product, suchas a fabric softener, laundry detergent, or hard surface cleaner.

In some embodiments, the disclosed composition is incorporated in apreservative or in a personal care system in a concentration (by totalweight) of e.g., 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%,5.5%, 6%, 6.5%, 7%, 6.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%,12%, 12.5%, 13%, 13.5%, 14%, 14.5%, or 15%, including any value andrange therebetween.

As used herein, the phrase “personal care” refers to compositions thatcan be formulated in various cosmetic and pharmaceutical consumerproducts utilizing a variety of delivery systems and carrier bases. Suchconsumer product forms include, but are not limited to, shampoos,aftershaves, sunscreens, body and hand lotions, skin creams, liquidsoaps, bar soaps, bath oil bars, shaving creams, conditioners, permanentwaves, hair relaxers, hair bleaches, hair detangling lotion, stylinggel, styling glazes, spray foams, styling creams, styling waxes, stylinglotions, mousses, spray gels, pomades, shower gels, bubble baths, haircoloring preparations, conditioners, hair lighteners, coloring andnon-coloring hair rinses, hair grooming aids, hair tonics, spritzes,styling waxes, Band-Aids, and balms.

In some embodiments, the disclosed formulation is in the form of, or apart of, a cream, an ointment, a paste, a gel, a lotion, a milk, an oil,a suspension, a solution, an aerosol, a spray, a foam, or a mousse.

Ointments are semisolid preparations, typically based on petrolatum orpetroleum derivatives. The specific ointment base to be used is one thatprovides for optimum delivery for the active agent chosen for a givenformulation, and, preferably, provides for other desired characteristicsas well (e.g., emolliency). As with other carriers or vehicles, anointment base should be inert, stable, nonirritating and nonsensitizing.As explained in Remington: The Science and Practice of Pharmacy, 19thEd., Easton, Pa.: Mack Publishing Co. (1995), pp. 1399-1404, ointmentbases may be grouped in four classes: oleaginous bases; emulsifiablebases; emulsion bases; and water-soluble bases. Oleaginous ointmentbases include, for example, vegetable oils, fats obtained from animals,and semisolid hydrocarbons obtained from petroleum. Emulsifiableointment bases, also known as absorbent ointment bases, contain littleor no water and include, for example, hydroxystearin sulfate, anhydrouslanolin and hydrophilic petrolatum. Emulsion ointment bases are eitherwater-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, andinclude, for example, cetyl alcohol, glyceryl monostearate, lanolin andstearic acid. Exemplary water-soluble ointment bases are prepared frompolyethylene glycols of varying molecular weight.

Lotions are preparations that are to be applied to the skin surfacewithout friction. Lotions are typically liquid or semiliquidpreparations in which solid particles, including thesunscreens-containing microcapsules, are present in a water or alcoholbase. Lotions are typically preferred for covering/protecting large bodyareas, due to the ease of applying a more fluid composition. Lotions aretypically suspensions of solids, and oftentimes comprise a liquid oilyemulsion of the oil-in-water type. It is generally necessary that theinsoluble matter in a lotion be finely divided. Lotions typicallycontain suspending agents to produce better dispersions as well ascompounds useful for localizing and holding the active agent in contactwith the skin, such as methylcellulose, sodium carboxymethyl-cellulose,and the like.

In some embodiment, the personal care system comprises an ionicformulation. In some embodiment, the personal care system comprises acationic formulation. In some embodiment, the personal care systemcomprises a natural formulation.

Creams are viscous liquids or semisolid emulsions, either O/W or W/O.Cream bases are typically water-washable, and contain an oil phase, anemulsifier and an aqueous phase. The oil phase, also called the“internal” phase, generally comprises petrolatum and/or a fatty alcoholsuch as cetyl or stearyl alcohol. The aqueous phase typically, althoughnot necessarily, exceeds the oil phase in volume, and generally containsa humectant. The emulsifier in a cream formulation is generally anonionic, anionic, cationic or amphoteric surfactant. Reference may bemade to Remington: The Science and Practice of Pharmacy, supra, forfurther information.

Pastes are semisolid dosage forms in which the bioactive agent issuspended in a suitable base. Depending on the nature of the base,pastes are divided between fatty pastes or those made from asingle-phase aqueous gel. The base in a fatty paste is generallypetrolatum, hydrophilic petrolatum and the like. The pastes made fromsingle-phase aqueous gels generally incorporate carboxymethylcelluloseor the like as a base. Additional reference may be made to Remington:The Science and Practice of Pharmacy, for further information.

Gel formulations are semisolid, suspension-type systems. Single-phasegels contain organic macromolecules distributed substantially uniformlythroughout the carrier liquid, which is typically aqueous, but also,preferably, contain an alcohol and, optionally, an oil. Preferredorganic macromolecules, i.e. gelling agents, are crosslinked acrylicacid polymers such as the family of carbomer polymers, e.g.,carboxypolyalkylenes that may be obtained commercially under thetrademark Carbopol™. Other types of preferred polymers in this contextare hydrophilic polymers such as polyethylene oxides,polyoxyethylene-polyoxypropylene copolymers and polyvinylalcohol;cellulosic polymers such as hydroxypropyl cellulose, hydroxyethylcellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulosephthalate, and methyl cellulose; gums such as tragacanth and xanthangum; sodium alginate; and gelatin. In order to prepare a uniform gel,dispersing agents such as alcohol or glycerin can be added, or thegelling agent can be dispersed by trituration, mechanical mixing orstirring, or combinations thereof.

Sprays generally provide the active agent in an aqueous and/or alcoholicsolution which can be misted onto the skin for delivery. Such spraysinclude those formulated to provide for concentration of the activeagent solution at the site of administration following delivery, e.g.,the spray solution can be primarily composed of alcohol or other likevolatile liquid in which the active agent can be dissolved. Upondelivery to the skin, the carrier evaporates, leaving concentratedactive agent at the site of administration.

Foam compositions are typically formulated in a single or multiple phaseliquid form and housed in a suitable container, optionally together witha propellant which facilitates the expulsion of the composition from thecontainer, thus transforming it into a foam upon application. Other foamforming techniques include, for example the “Bag-in-a-can” formulationtechnique. Compositions thus formulated typically contain a low-boilinghydrocarbon, e.g., isopropane. Application and agitation of such acomposition at the body temperature cause the isopropane to vaporize andgenerate the foam, in a manner similar to a pressurized aerosol foamingsystem. Foams can be water-based or hydroalcoholic, but are typicallyformulated with high alcohol content which, upon application to the skinof a user, quickly evaporates, driving the active ingredient through theupper skin layers to the site of treatment.

Personal care formulations can further include, without limitation,human body or hair deodorizing solution, deodorizing gel, deodorizingspray, deodorizing stick, deodorizing roll-on, deodorizing paste,deodorizing cream, deodorizing lotion, deodorizing aerosol, and othercommonly marketed human body and commonly marketed animal and petdeodorizing compositions.

Additional cosmetically or pharmaceutically beneficial (active)ingredients can also be included in the formulations of the presentinvention, which can be selected from, but are not limited to, skincleansers, cationic, anionic surfactants, non-ionic surfactants,amphoteric surfactants, and zwitterionic surfactants, skin and hairconditioning agents, vitamins, hormones, minerals, plant extracts,anti-inflammatory agents, collagen and elastin synthesis boosters,UVA/UVB sunscreens, concentrates of plant extracts, emollients,moisturizers, skin protectants, humectants, silicones, skin soothingingredients, antimicrobial agents, antifungal agents, treatment of skininfections and lesions, blood microcirculation improvement, skin rednessreduction benefits, additional moisture absorbents, analgesics, skinpenetration enhancers, solubilizers, moisturizers, emollients,anesthetics, colorants, perfumes, preservatives, seeds, broken seed nutshells, silica, clays, beads, luffa particles, polyethylene balls, mica,pH adjusters, processing aids, and combinations thereof.

In some embodiments of the present invention, the formulation ischaracterized by resistance to discoloration.

As used herein, “discoloration” is defined as change in the hue or inthe visual appearance of a formulation, due to an internal reactionamong its constituents or the bleaching or oxidation action caused by acombination of factors that include, but are not limited to, air, hightemperature, humidity, ultraviolet exposure e.g., sunlight.

Articles Comprising the Formulations

According to an aspect of some embodiments of the present inventionthere is provided an article which comprises any one of the personalcare formulation described herein.

Some embodiments of this aspect of present embodiments are includedhereinabove, under “Exemplary Formulations”, and form an integral partof embodiments relating to “Articles comprising the Formulation”.

According to an aspect of some embodiments of the present invention,there is provided a pharmaceutical, cosmetic or cosmeceutical productcomprising the formulation described in any of their respectiveembodiments herein, for use in treating a medical, cosmetic orcosmeceutic condition, as described herein.

According to an aspect of some embodiments of the present invention, theformulation described in any of their respective embodiments herein isused as, or a part of, a preservative in any pharmaceutical, cosmetic orcosmeceutical product or in any article as describe herein.

As used herein, “preservative” is used to prevent the growth ofbacteria, fungi and/or molds in any personal care composition orformulation.

According to a further aspect of some embodiments of the presentinvention, there is provided a use of the formulation described hereinin the manufacture of a pharmaceutical, cosmetic or cosmeceuticalproduct, which can be used in treating a medical, cosmetic orcosmeceutic condition, as described herein.

In some embodiments, there is provided a method of treating a medical,cosmeceutical or cosmetic condition treatable by a topical ortransdermal administration, the method comprising topically applying theformulation described herein (e.g., in the context of a pharmaceutical,cosmetic or cosmeceutic product) to a skin or mucosal tissue of asubject afflicted by the condition.

The phrases “topical” “topical administrations” and or any grammaticalderivative thereof, is meant to encompass applications, which include,without limitation, dermal applications, ophthalmic application, vaginalapplication, rectal application and intranasal application.

Medical, cosmetic or cosmeceutical conditions that can benefit fromcontaining the formulations described herein when applied topically,with or without an additional active ingredient, include, but are notlimited to, infections caused by pathogenic microorganisms, as discussedin further detail hereinbelow, wounds, particularly when associated withan infection, acne, skin infections, viral blisters such as one causedby herpes, sexual dysfunction such as erectile dysfunction.

Hence, according to some embodiments of the present invention, thepharmaceutical, cosmetic or cosmeceutical formulation or product furthercomprises an antimicrobial agent, as an additional pharmaceuticallyactive agent.

Microbial infections include any infection caused by a pathogenicmicroorganism, including, bacterial infection, fungal infection,protozoal infection, viral infection and the like, e.g., molluscumcontagiosum (a viral infection of the skin or occasionally of the mucousmembranes), fungal nail infections, and cutaneous leishmaniasis.

Topical bodily sites include skin, mucosal tissue, eye, ear, nose,mouth, rectum and vagina.

In some embodiments, there is provided an article (e.g., a medicaldevice such as a bandage or adhesive patch), a formulation, or aproduct, as described herein, configured for topical application,whereby a condition treatable by such as article, product or formulationis an infection caused by a microorganism.

In some embodiments of the present invention, the article is e.g., afabric, a bandage, a wipe (e.g., a wet wipe), a pledget, a swab, asuppository, a dressing, a solution, a mousse, a pad, or a patch.

In some exemplary embodiments of the present invention, the article isin the form of paste, cream, lotion, foam, gel, emulsion, an ointment,or soap.

In some embodiments, the personal care formulation of the presentinvention can be used to treat skin tissue or on damaged or unhealthyskin tissue.

The phrase “damaged or unhealthy skin tissue” as used herein refers to adeviation from healthy functional skin tissue. In the case of skin—askin that is weaker, less elastic, and is more prone to injury thanhealthy skin. The structure of unhealthy or damaged skin is inferior tothat of healthy skin (for example, the dermis and epidermis containfewer cells and collagen).

The phrase “healthy skin tissue” as used herein refers to skin that isstrong, elastic, smooth and plump. One purpose of treating healthy skinis to prevent deterioration of skin induced by aging or environmentalstress including, but not limited to, microbial infection.

The term “damaged” as used herein, or any grammatical derivativethereof, refers broadly to injuries to the skin and subcutaneous tissueas well as internal organs initiated in any one of a variety of ways(e.g., pressure sores from extended bed rest, wounds induced by trauma,wounds received during or following a surgical procedure and the like)and with varying characteristics. Examples include, but are not limitedto, bruises, scrapes, burn wounds, sunburn wounds, incisional wounds,excisional wounds, surgical wounds, necrotizing fascitis, ulcers, venousstasis ulcers, diabetic ulcers, decubitus ulcers, aphthous ulcers,pressure ulcers, scars, alopecia areata, dermatitis, allergic contactdermatitis, atopic dermatitis, berloque dermatitis, diaper dermatitis,dyshidrotic dermatitis, psoriasis, eczema, erythema, warts, anal warts,angioma, cherry angioma, athlete's foot, atypical moles, basal cellcarcinoma, Bateman's purpura, bullous pemphigoid, Candida,chondrodermatitis helicis, Clark's nevus, cold sores, condylomata,cysts, Darier's disease, dermatofibroma, Discoid Lupus Erythematosus,nummular eczema, atopic eczema, dyshidrotic eczema, hand eczema,Multiforme Erythema Nodosum, Fordyce's Condition, FolliculitisKeloidalis Nuchae, Folliculitis, Granuloma Annulare, Grover's Disease,heat rash, herpes simplex, herpes zoster (shingles), HidradenitisSuppurativa, Hives, Hyperhidrosis, Ichthyosis, Impetigo, KeratosisPilaris, Keloids, Keratoacanthoma, Lichen Planus, Lichen Planus LikeKeratosis, Lichen Simplex Chronicus, Lichen Sclerosus, LymphomatoidPapulosis, Lupus of the Skin, Lyme Disease, Lichen Striatus, MyxoidCysts, Mycosis Fungoides, Molluscum Contagiosum, Moles, Nail Fungus,Necrobiosis Lipoidica Diabeticorum, Nummular Dermatitis, Onychoschizia,Onychomycosis, Pityriasis Lichenoides, Pityriasis Rosea, PityriasisRubra Pilaris, Plantar Warts, Poison Ivy, Poison Oak, Pompholyx,Pseudofolliculitis Barbae, Pruritus Ani and Pityriasis Alba.

Antimicrobial Activity

According to an aspect of some embodiments of the present inventionthere is provided a method of inhibiting or reducing or retarding theformation of load of a microorganism and/or the formation of a biofilm,in and/or on an article. The method comprises incorporating in and/or onthe article any one of the formulations disclosed herein, including anyof the respective embodiments thereof. The article can be any one of thearticles described herein.

Such articles take advantage of the improved antimicrobial activityexhibited by the formulations as described herein.

In some embodiments, the components in the formulation act in synergism.

In some embodiments, the term synergism, or any grammatical derivativethereof, is defined as the simultaneous action of two or more compoundsin which the total response of an organism to the combination is greaterthan the sum of the individual components. Although many combinations ofantimicrobial compounds have been studied, a synergistic effect israrely revealed and the global use of antimicrobial combinations withsynergistically enhanced activity is rather limited.

Some embodiments of this aspect of present embodiments are includedhereinabove, under “Exemplary Formulations”, and under “Articlescomprising the Formulation” and form an integral part of embodimentsrelating to “Antimicrobial Activity”.

Herein “antimicrobial activity” is referred to as an ability to inhibit(prevent), reduce or retard bacterial growth, fungal growth, biofilmformation or eradicate living bacterial cells, or their spores, orfungal cells or viruses in a suspension or in a moist environment.

Herein, inhibiting or reducing or retarding the formation of load of amicroorganism refers to inhibiting, reducing, or retarding growth ofmicroorganisms and/or eradicating a portion or all of an existingpopulation of microorganisms. Thus, formulations described herein can beused both in reducing the formation of microorganisms on or in anarticle, and in killing microorganisms in or on an article or a livingtissue.

The microorganism can be, for example, a unicellular microorganism(prokaryotes, archaea, bacteria, eukaryotes, protists, fungi, algae,molds, yeast, euglena, protozoan, dinoflagellates, apicomplexa,trypanosomes, amoebae and the likes), or a multicellular microorganism.

An article, according to these embodiments, can be also a living tissue,for example, a skin or mucosal tissue, as described herein.

In the context of the present embodiments, the formulations, articlesand methods described herein may be used to produce cell inhibitingsurface, or a microbial cell killing surface, that remains active forextended periods. Such an antimicrobial surface may not need anadditional treatment with antimicrobial compositions, clean-uptreatments to effect decontamination and cosmetic painting, therebysimplifying upkeep of the physical condition and appearance of microbialinfestation prone surfaces. It is contemplated that in some embodiments,the formulations of the present invention may be easily applied tosusceptible surfaces in advance of and/or during exposure to a microbialorganism.

In some embodiments, the microorganism comprises bacterial cells ofbacteria such as, for example, Gram-positive and Gram-negative bacteria.

In some embodiments, the Gram-positive bacteria are Staphylococcusaureus, Bacillus cereus and Staphylococcus epidermidis.

In some embodiments, the Gram-negative bacteria are Escherichia coli andPseudomonas aeuruginosa.

In some embodiments of the present invention, the microorganism is fungie.g., Candida albicans and Aspergillus niger.

The term “biofilm”, as used herein, refers to an aggregate of livingcells which are stuck to each other and/or immobilized onto a surface ascolonies. The cells are frequently embedded within a self-secretedmatrix of extracellular polymeric substance (EPS), also referred to as“slime”, which is a polymeric sticky mixture of nucleic acids, proteinsand polysaccharides.

In the context of the present embodiments, the living cells forming abiofilm can be cells of a unicellular microorganism (prokaryotes,archaea, bacteria, eukaryotes, protists, fungi, algae, euglena,protozoan, dinoflagellates, apicomplexa, trypanosomes, amoebae and thelikes), or cells of multicellular organisms in which case the biofilmcan be regarded as a colony of cells (like in the case of theunicellular organisms) or as a lower form of a tissue.

In the context of the present embodiments, the cells are ofmicroorganism origins, and the biofilm is a biofilm of microorganisms,such as bacteria and fungi. The cells of a microorganism growing in abiofilm are physiologically distinct from cells in the “planktonic form”of the same organism, which by contrast, are single-cells that may floator swim in a liquid medium. Biofilms can go through several life-cyclesteps which include initial attachment, irreversible attachment, one ormore maturation stages, and dispersion.

The phrase “antibiofilm formation activity” refers to the capacity of asubstance to affect the prevention of formation of a biofilm ofbacterial, fungal and/or other cells, and/or to affect a reduction inthe rate of buildup of a biofilm of bacterial, fungal and/or othercells, on a surface of a substrate. This activity is also referred toherein as anti-biofouling activity, or antifouling activity.

As used herein, the term “preventing” in the context of antimicrobial,indicates that the growth rate of the microorganism cells is essentiallynullified or is reduced by at least 20%, at least 30%, at least 40%, atleast 50%, at least 60%, at least 70%, at least 80%, at least 90%,including any value there between, of the appearance of themicroorganism in a comparable situation lacking the presence offormulation or an article containing same. Alternatively, preventingmeans a reduction to at least 15%, 10%, or 5% of the appearance of themicroorganism cells in a comparable situation lacking the presence ofthe formulation or an article containing same.

Methods for determining a level of appearance of a microorganism cellsare known in the art.

General:

As used herein the term “about” refers to ±10%.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean “including but not limited to”.

The term “consisting of” means “including and limited to”.

The term “consisting essentially of” means that the composition, methodor structure may include additional ingredients, steps and/or parts, butonly if the additional ingredients, steps and/or parts do not materiallyalter the basic and novel characteristics of the claimed formulation,method or structure.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals therebetween.

As used herein the term “method” refers to manners, means, techniquesand procedures for accomplishing a given task including, but not limitedto, those manners, means, techniques and procedures either known to, orreadily developed from known manners, means, techniques and proceduresby practitioners of the chemical, pharmacological, biological,biochemical and medical arts.

As used herein, the term “treating” includes abrogating, substantiallyinhibiting, slowing or reversing the progression of a condition,substantially ameliorating clinical or aesthetical symptoms of acondition or substantially preventing the appearance of clinical oraesthetical symptoms of a condition.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

Various embodiments and aspects of the present invention as delineatedhereinabove and as claimed in the claims section below find experimentalsupport in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with theabove descriptions illustrate some embodiments of the invention in anon-limiting fashion.

General Procedure

In additional exemplary procedures, the products were inoculated with1—Bacteria: Escherichia coli, Staphylococcus aureus and Pseudomonasaeruginosa, 2—Yeast: Candida albicans and 3—Fungi: Aspergillusbrasiliensis (niger). Each item of the 5 tested microorganism wasinoculated by one of the 5 different microorganisms cited, as indicatedin: USP 35, 2013, chapter: 51, Antimicrobial effectiveness testing.

Five samples of the product were inoculated with 1 microorganism each.The volume of the culture was calculated to yield a count of 10⁵-10⁶CFU/gr (CFU; colony-forming units).

The efficacy of was determined according to Antimicrobial PreservationAppendix XVI C. British, European Pharmacopea 2010.

In additional exemplary procedures, 20 gr sample from each item weretested 2, 7, 14, 21, and 28 days after inoculation.

In additional exemplary procedures, the test was also performedaccording to S.O.P 122: “Preservative Efficacy Challenge Test”.

In additional exemplary procedure, minimum inhibitory concentration(MIC) evaluation test with Candida albicans was performed in test tubes.Growth in this case is visually evaluated. A pure culture of a singlemicroorganism was grown in Tryptic soy broth, or sabouraud broth foryeast and mold.

In another exemplary procedure, MIC evaluation test with A. niger wasperformed in test tubes. Growth in this case is visually evaluated. Apure culture of a single microorganism was grown in Tryptic soy broth,or sabouraud broth for yeast and mold.

The culture is standardized using standard microbiological techniques tohave a concentration of very near 1 million cells per milliliter.

The antimicrobial agent is diluted a number of times, with Tryptic soybroth or sabouraud broth for fungi. After the antimicrobial agent hadbeen diluted, a volume of the standardized inoculums was added to eachdilution vessel, bringing the microbial concentration to approximately1,000,000 cells per milliliter. The inoculated, serially dilutedantimicrobial agent was incubated at an appropriate temperature for thetest organism, 24 hours for bacteria 48 for yeast and 72 for mold.

After incubation, the series of dilution vessels was observed formicrobial growth, usually indicated by turbidity and/or a pellet ofmicroorganisms in the bottom of the vessel. The last tube in thedilution series that does not demonstrate growth corresponds with theMIC of the antimicrobial agent. MIC results are expressed in ppm.

The microorganism strains used for the test were E. coli ATCC 8739, P.aeruginosa ATCC 9027, S. aureus ATCC 6538, C. albicans ATCC 10231, A.niger ATCC 16404.

Example 1 Anti Microbial Activity Evaluation

Exemplary formulations and antimicrobial results (MIC; relativeefficacy) are presented in Table 1 below, showing the superiorantimicrobial activity of the disclosed formulations.

TABLE 1 Microorganism/Preservative S. aureus E. coli P. aeruginosa A.niger C. albicans Maltol 3800 4000 <1350 3150 2250 Ethyl LauroylArginate 500 2500 5000 20000 10000 Maltol = 97% <300 400 600 600 400Ethyl Lauroyl Arginate = 3%   Maltol = 97% <360 >1200 1200 720 <360Stearamidopropyl dimethylamine = 3%      Maltol = 95% <360 >1200 1200720-960 <360 Stearamidopropyl dimethylamine = 5%      Maltol = 95% <3601200 Hexadecylpyridinium chloride monohydrate = 5%    Maltol = 95% <360600 Benzyldimethyldodecylammonium chloride = 5%   Maltol = 97% <200 800700 800 600 Benzyldimethyldodecylammonium chloride = 3%  Maltol = 95%600 <360 Hexadimethrine Bromide = 5%   Maltol = 97% 600 1100 400 20001000 Hexadimethrine Bromide = 3%   Maltol = 95% >1200 ~1200Cocoamidopropyl betaine = 5%   Maltol = 95% >1200 1200 Lauryl betaine =5%      Maltol = 95% >1200 >1200 Hydroxycetyl hydroxyethyl dimoniumchloride = 5%  Maltol = 95% 600 1200 Myristamidopropyl dimethylaminechloride = 5%  Maltol = 95% 1200 1200 N-[3-(Dimethylamino) propyl]lauramide = 5%    Maltol = 95% <360 1200 Hexadecyltrimethylammoniumchloride = 5%  Maltol = 95% 22 45 180 22 22 Didecyldimethylammoniumchloride = 5%  Maltol = 95% 360 360 960 360-480 <60Dimethyldioctylammonium chloride = 5%  Maltol = 95% 720 960600 >1200 >1200 Dimethyldioctadecylammonium chloride = 5%   Maltol = 95%960 960 Dodecyltrimethylammonium chloride = 5% Benzyldimethyldodecylammonium <60 <60 120 <60 <60 chlorideDidecyldimethylammonium chloride <3 <3 15 <30 <30 Maltol = 95% 22 45 18022 22 Didecyldimethylammonium chloride = 5%  Polyquaternium-2 <60 <60 602000 <60 Polyquaternium-80 120 360 >600 120 240 Dodecyltrimethylammoniumchloride <60 <60 360 360 <60 Maltol = 95% <120 <120 240 200 <100Polyquaternium-2 = 2.5%      Didecyldimethylammonium chloride = 2.5% Maltol = 95% 360 480 720 400 100 Polyquaternium-2 = 2.5%     Benzyldimethyldodecylammonium chloride = 2.5%  Maltol = 95% 1000Polyquaternium-2 = 2.5%      Dodecyltrimethylammonium chloride = 2.5% Maltol = 95% <60 <60 <60 360-480 <60     DDAC = 5% (pH = 4) Maltol = 95%<60 <60 360 120-360 <60      DDAC = 5% (pH = 5.5) Maltol = 95% <60 120360 360 360     DDAC = 5% (pH = 7) Maltol = 95% <60 <60 120 <60 <60    DDAC = 5% (pH = 9) Maltol = 95% 480 480 1200 960 600Polyquaternium-80 = 5%       Maltol = 95% >1200 >1200 >1200 1200 <360Polyquaternium-11 = 5%       Maltol = 95% 960-1200 960-1200 480~1200-1300  480 Polyquaternium-2 = 5%     

Example 2 Preservative Effectiveness (Challenge Tests)

In another exemplary procedure, the antimicrobial preservativeeffectiveness was tested to measure the efficiency of the preservatives.

Method: The method applied was based on the USP 35 guidelines forantimicrobial effectiveness testing. Five samples of the product wereinoculated with 1 microorganism each. The volume of the culture wascalculated to yield a count of 10⁵-10⁶ CFU/gr. A 4 weeks follow-up isperformed. Each product was sampled once a week and a viable count wasperformed. Polysorbate 20 and Soy Lecithin were added to the culturemedia in order to neutralize the preservatives and to enable therecovery of all living microorganisms.

The antimicrobial tests are shown in Tables 2A-G.

In exemplary procedures, neutral base cream was preserved with 0.3% of apreservative comprising: maltol (95%), and didecyldimethylammoniumchloride (5%).

The neutral base cream formulation comprises: water demineralized(82.8%), glycerin (4%), caprylic/capric triglycerides (3%), cetearylglucoside and cetearyl alcohol (5%), cetearyl alcohol and Ceteareth-20(4.8%), tocopheryl acetate (0.1%).

The results are summarized in Table 2A.

TABLE 2A Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum   1* 10⁶   1* 10⁶   1* 10⁶   1* 10⁵   1* 10⁵  2 days 6.7*10⁴ 4.5* 10⁴ 6.5* 10³   3* 10² 6.4* 10³  7 days <10 <10 <10 4.1* 10³5.6* 10⁴ 14 days <10 <10 <10 5.5* 10² 8.8* 10³ 21 days <10 <10 <10 <10  8* 10³ 28 days <10 <10 <10 <10   8* 10³

In additional exemplary procedures, neutral base cream was preservedwith 0.3% of a preservative comprising: Maltol (95%), andbenzyldimethyldodecylammonium chloride (5%).

The neutral base cream formulation comprises: water demineralized(82.8%), glycerin (4%), caprylic/capric triglycerides (3%), cetearylglucoside and cetearyl alcohol (5%), cetearyl alcohol and Ceteareth-20(4.8%), tocopheryl acetate (0.1%).

The results are summarized in Table 2B.

TABLE 2B Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum   1* 10⁶   1* 10⁶   1* 10⁶   1* 10⁵   1* 10⁵  2 days <103.1* 10³ 1.2* 10⁵   8* 10²   1* 10⁴  7 days 4.4* 10⁴ <10 1.3* 10⁵ 5.2*10² 6.7* 10⁴ 14 days <10 <10   5* 10³ <10   7* 10⁴ 21 days <10 <10 <10<10 5.5* 10⁴ 28 days <10 <10 <10 <10   5* 10⁴

In additional exemplary procedures, cationic conditioner preserved with0.3% of a preservative comprising: maltol (95%), anddidecyldimethylammonium chloride (5%). The cationic conditionerformulation comprises: water demineralized (85.7%), glycerin (3%),caprylic/capric triglycerides (3%), tetearyl glucoside and cetearylalcohol (2%), cetearyl alcohol and Ceteareth-20 (5%), behetrimoniumchloride (1%).

The results are summarized in Table 2C.

TABLE 2C Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum   1* 10⁶   1* 10⁶   1* 10⁶   1* 10⁵   1* 10⁵  2 days 1.1*10⁵ 5.1* 10⁴ 7.3* 10³ 2.5* 10²   3* 10⁴  7 days <10 <10 5.2* 10³ 2.8*10² 5.5* 10⁴ 14 days <10 <10   3* 10² <10 5.5* 10⁴ 21 days <10 <10 <10<10   5* 10⁴ 28 days <10 <10 <10 <10 4.6* 10⁴

In additional exemplary procedures, anionic shampoo was preserved with0.3% of a preservative comprising: maltol (95%), anddidecyldimethylammonium chloride (5%).

The anionic shampoo formulation comprises: water demineralized (78.8%),glycerin (0.3%), citric acid (0.1%), cocamidopropyl betaine (1%),cocamide diethanolamine (DEA) (1%), Sodium Laureth Sulphate (SLES)(15%), Sodium chloride (3.5%). The results are summarized in Table 2D.

TABLE 2D Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum 1* 106 1* 106 1* 106   1* 105   1* 105  2 days 4.4* 1043.5* 103 1* 105 3.5* 104 5.8* 103  7 days <10 <10 <10 4.6* 104 2.8* 10414 days <10 <10 <10 3.3* 103 3.5* 103 21 days <10 <10 <10 <10   7* 10228 days <10 <10 <10 <10   5* 102

In additional exemplary procedures, anionic shampoo was preserved with0.4% of a preservative comprising: maltol (95%), didecyldimethylammoniumchloride (2.5%) and Polyquaternium-2 (2.5%).

The anionic shampoo formulation comprises: water demineralized (78.7%),glycerin (0.3%), citric acid (0.1%), cocamidopropyl betaine (1%),cocamide diethanolamine (DEA) (1%), Sodium Laureth Sulphate (SLES)(15%), Sodium chloride (3.5%). The results are summarized in Table 2E.

TABLE 2E Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum 1* 10⁶ 1* 10⁶ 1* 10⁶ 1* 10⁵   1* 10⁵  2 days <10 <10 <10<10 3.3* 10⁴  7 days <10 <10 <10 <10 5.5* 10³ 14 days <10 <10 <10 <10<10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

It can be concluded that the tested product meets the EP and USPcriteria for cosmetics.

In additional exemplary procedures, anionic shampoo was preserved with0.5% of a preservative comprising: maltol (90%), and Polyquaternium-2(10%).

The anionic shampoo formulation comprises: water demineralized (78.6%),glycerin (0.3%), citric acid (0.1%), cocamidopropyl betaine (1%),cocamide diethanolamine (DEA) (1%), Sodium Laureth Sulphate (SLES)(15%), Sodium chloride (3.5%). The results are summarized in Table 2F.

TABLE 2F Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum 1* 10⁶ 1* 10⁶ 1* 10⁶ 1* 10⁵   1* 10⁵  2 days <10 <10 <10<10 3.8* 10⁴  7 days <10 <10 <10 <10   3* 10² 14 days <10 <10 <10 <10 3* 10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

It can be concluded that the tested product meets the EP and USPcriteria for cosmetics.

In additional exemplary procedures, anionic shampoo was preserved with0.5% of a preservative comprising: maltol (90%), Polyquaternium-2 (5%)and Polyquaternium-80 (5%).

The anionic shampoo formulation comprises: water demineralized (78.6%),glycerin (0.3%), citric acid (0.1%), cocamidopropyl betaine (1%),cocamide diethanolamine (DEA) (1%), Sodium Laureth Sulphate (SLES)(15%), Sodium chloride (3.5%). The results are summarized in Table 2G.

TABLE 2G Time of reading E. Coli S. Aureus P. aeruginosa C. albicans A.niger Inoculum 1* 10⁶ 1* 10⁶ 1* 10⁶ 1* 10⁵ 1* 10⁵  2 days <10 <10 <10<10 4* 10⁴  7 days <10 <10 <10 <10 5* 10² 14 days <10 <10 <10 <10 <10 21days <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

It can be concluded that the tested product meets the EP and USPcriteria for cosmetics.

-   -   * The numbers in Tables 2A-C represent CFU/ per 1 ml or per 1        mg; the tests of E. coli, S. aureus, and P. aeruginosa were        performed at 30° C. The tests of C. albicans, A. niger were        performed at 26° C.

Example 3 Anti Microbial Activity Evaluation And PreservativeEffectiveness (Challenge Tests)

Exemplary formulations and antimicrobial results (MIC; relativeefficacy) are presented. The antimicrobial preservative effectiveness ofthe disclosed formulations was tested to measure the efficiency of thepreservatives.

Formulation 3A

Table 3 shows the antimicrobial activity results of formulation 3A.

TABLE 3 Preservative E. coli S. aureus P. aeruginosa C. albicans A.niger      Maltol = 95%, <120 <120 240 <100 200 Polyquaternium-2 = 2.5%,Didecyldimethylammonium chloride (DDAC) = 2.5%

In additional exemplary procedures, neutral base cream was preservedwith 0.5% of a preservative comprising Formulation 3A, comprising:maltol (95%), Polyquaternium-2 (2.5%), and didecyldimethylammoniumchloride (DDAC) (2.5%).

The neutral base cream formulation comprises: water demineralized(82.8%), glycerin (4%), caprylic/capric triglycerides (3%), cetearylglucoside and cetearyl alcohol (5%), cetearyl alcohol and Ceteareth-20(4.8%), tocopheryl acetate (0.1%).

The results are summarized in Table 4.

TABLE 4 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1 × 10∧6 1 × 10∧6 1.1 × 10∧6 1 × 10∧5 1 × 10∧5  2 days<10 <10 <10 <10 <10  7 days <10 <10 <10 <10 <10 14 days <10 <10 <10 <10<10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

In additional exemplary procedures, anionic shampoo was preserved with0.4% of a preservative comprising Formulation 3A.

The anionic shampoo formulation comprises: water demineralized (78.7%),glycerin (0.3%), citric acid (0.1%), cocamidopropyl betaine (1%),cocamide diethanolamine (DEA) (1%), Sodium Laureth Sulphate (SLES)(15%), Sodium chloride (3.5%).

The results are summarized in Table 5.

TABLE 5 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1 × 10{circumflex over ( )}6 1 × 10{circumflex over ( )}61.1 × 10{circumflex over ( )}6 1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days <10 <10 <10 <10 3.3 × 10{circumflexover ( )}4  7 days <10 <10 <10 <10 5.5 × 10{circumflex over ( )}3 14days <10 <10 <10 <10 <10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10<10 <10

Formulation 3B

Table 6 shows the antimicrobial activity results of formulation 3B.

TABLE 6 A. Preservative E. coli S. aureus P. aeruginosa C. albicansniger Maltol = 90% 480 <240 1200 600 800 Polyquaternium- 80 = 10%

In additional exemplary procedures, anionic shampoo previously describedwas preserved with 0.5% of a preservative comprising Formulation 3B,comprising: maltol (90%) and Polyquaternium-80 (10%).

The results are summarized in Table 7.

TABLE 7 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days <10 <10 <10  10 4.5 × 10{circumflexover ( )}4  7 days <10 <10 <10 <10 2.2 × 10{circumflex over ( )}2 14days <10 <10 <10 <10 <10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10<10 <10

In additional exemplary procedures, neutral base cream previouslydescribed was preserved with 0.5% of a preservative comprisingFormulation 3B

The results are summarized in Table 8.

TABLE 8 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days  10 <10  10 <10 4.3 × 10{circumflexover ( )}4  7 days <10 <10 <10 <10 6.7 × 10{circumflex over ( )}3 14days <10 <10 <10 <10   3 × 10{circumflex over ( )}1 21 days <10 <10 <10<10   2 × 10{circumflex over ( )}1 28 days <10 <10 <10 <10 <10

Formulation 3C

Table 9 shows the antimicrobial activity results of formulation 3C.

TABLE 9 A. Preservative E. coli S. aureus P. aeruginosa C. albicansniger Maltol = 90% 400 <200 400 800 800 Polyquaternium- 2 = 10%

In additional exemplary procedures, neutral base cream previouslydescribed was preserved with 0.5% of a preservative comprisingFormulation 3C, comprising: maltol (90%), and Polyquaternium-2 (10%).

The results are summarized in Table 10.

TABLE 10 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days  10 <10 <10  10 6.3 × 10{circumflexover ( )}4  7 days <10 <10 <10 <10 8.5 × 10{circumflex over ( )}3 14days <10 <10 <10 <10 5.3 × 10{circumflex over ( )}2 21 days <10 <10 <10<10 2.1 × 10{circumflex over ( )}2 28 days <10 <10 <10 <10   5 ×10{circumflex over ( )}1

In additional exemplary procedures, anionic shampoo previously describedwas preserved with 0.5% of a preservative comprising Formulation C.

The results are summarized in Table 11.

TABLE 11 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days <10 <10 <10 <10 3.8 × 10{circumflexover ( )}4  7 days <10 <10 <10 <10   3 × 10{circumflex over ( )}2 14days <10 <10 <10 <10   3 × 10{circumflex over ( )}1 21 days <10 <10 <10<10 <10 28 days <10 <10 <10 <10 <10

Formulation 3D

Table 12 shows the antimicrobial activity results of formulation 3D.

TABLE 12 Preservative E. coli S. aureus P. aeruginosa C. albicans A.niger Maltol = 95% <100 200 400 <100 400 Polyquaternium-80 = 2.5%Didecyldimethylammonium chloride (DDAC) = 2.5%

In additional exemplary procedures, neutral base cream previouslydescribed was preserved with 0.5% of a preservative comprisingFormulation 3D, comprising: maltol (95%), didecyldimethylammoniumchloride (DDAC) (2.5%), and Polyquaternium-80 (2.5%).

The results are summarized in Table 13.

TABLE 13 Time of reading E. coli S. aureus P. aeruginosa C. albican A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5 1 ×10{circumflex over ( )}5  2 days <10 <10 <10 <10 <10  7 days <10 <10 <10<10 <10 14 days <10 <10 <10 <10 <10 21 days <10 <10 <10 <10 <10 28 days<10 <10 <10 <10 <10

In additional exemplary procedures, anionic shampoo previously describedwas preserved with 0.5% of a preservative comprising Formulation 3D.

The results are summarized in Table 14.

TABLE 14 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6 1 × 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5 1 ×10{circumflex over ( )}5  2 days <10 <10 <10 <10 1 × 10{circumflex over( )}4  7 days <10 <10 <10 <10  10 14 days <10 <10 <10 <10 <10 21 days<10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

Formulation 3E

Table 15 shows the antimicrobial activity results of formulation 3E.

TABLE 15 Preservative E. coli S. aureus P. aeruginosa C. albicans A.niger Maltol = 95%, <50 <50 100 <50 100 Didecyldimethylammonium chloride(DDAC) = 5%

In additional exemplary procedures, anionic shampoo previously describedwas preserved with 0.5% of a preservative comprising Formulation 3Ecomprising: maltol (95%), and didecyldimethylammonium chloride (DDAC)(5%).

The results are summarized in Table 16.

TABLE 16 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 1.1 × 10{circumflex over ( )}6   1× 10{circumflex over( )}6 1 × 10{circumflex over ( )}6 1.1 × 10{circumflex over ( )}5   1 ×10{circumflex over ( )}5  2 days   1 × 10{circumflex over ( )}5 4.8 ×10{circumflex over ( )}3 3 × 10{circumflex over ( )}4 1.5 ×10{circumflex over ( )}2 5.5 × 10{circumflex over ( )}3  7 days <10   2× 10{circumflex over ( )}1 1 × 10{circumflex over ( )}2   2 ×10{circumflex over ( )}1   6 × 10{circumflex over ( )}3 14 days <10 <10<10 <10 6.5 × 10{circumflex over ( )}3 21 days <10 <10 <10 <10 3.6 ×10{circumflex over ( )}3 28 days <10 <10 <10 <10   3 × 10{circumflexover ( )}3

Formulation 3F

Table 17 shows the antimicrobial activity results of formulation 3F.

TABLE 17 P. C. A. Preservative E. coli S. aureus aeruginosa albicansniger Maltol = 90%, 200 <100 1000 300 400 Suga Quat L-1010 (LAURDIMONIUMHYDROXYPROPYL DECYLGLUCOSIDES CHLORIDE) = 10%

In additional exemplary procedures, anionic shampoo previously describedwas preserved with 0.5% of a preservative comprising Formulation 3Fcomprising: maltol (90%), and Suga Quat L-1010(LAURDIMONIUMHYDROXYPROPYL DECYLGLUCOSIDES CHLORIDE) (10%)

The results are summarized in Table 18.

TABLE 18 Time of reading E. coli S. aureus P. aeruginosa C. albicans A.niger Inoculum 2.3 × 10{circumflex over ( )}5 1.3 × 10{circumflex over( )}5 1 × 10{circumflex over ( )}5 3 × 10{circumflex over ( )}4   1 ×10{circumflex over ( )}4  2 days   2 × 10{circumflex over ( )}3 <10 <10<10 1.7 × 10{circumflex over ( )}3  7 days   1 × 10{circumflex over( )}3 <10 <10 <10 1.5 × 10{circumflex over ( )}1 14 days  10 <10 <10 <10 10 21 days <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10

Formulation 3G

Table 19 shows the antimicrobial activity results of formulation 3Gcomprising: maltol (90%), and Cola Lipid C (Cocamidopropyl PG-DimoniumChloride Phosphate) (10%).

TABLE 19 Preservative E. coli S. aureus P. aeruginosa C. albicans A.niger Maltol = 90% 480 960 1200 480 960 Cola lipid C = 10%

In another exemplary procedure, the antimicrobial preservativeeffectiveness is tested to measure the efficiency of the preservative.

Example 4 Anti Microbial Activity Evaluation and PreservativeEffectiveness (Challenge Tests)

Further formulations comprising Maltol 90% to 98% and one or more of thefollowing cationic surfactants 1) to 12) is prepared: 1) Berberine CAS:2086-83-1; 2) Berberrubine; 3) Berberis vulgaris root extract CAS:84649-92-3/8054-40-8; 4) Isopropylbenzyl butylnorberberine iodide; 5)Palmatine cas: 3486-67-7; 6) Jatrorrhizine; 7) Coptisine; 8) Ungeremine;9) Epiberberine; 10) Pseudoberberine; 11) Stepharanine; 12) Sinapine

After determining the antimicrobial results (MIC; relative efficacy) ofeach formulation, the antimicrobial preservative effectiveness of thedisclosed formulations is tested as previously described to measure theefficiency of the preservatives.

In another exemplary procedure, the antimicrobial preservativeeffectiveness was tested to measure the efficiency of the preservatives.

Example 5 Maltol Shielding

Maltol has a metal chelating property. It can bond with metal ions andform a chelate product that can be strongly colored. This reaction ishighly likely to happen when maltol is used in a manufacturing processinvolving steel based equipment. It means that even small quantities ofthese chelates could induce an undesirable color in a finished cosmeticproduct.

A way to inhibit this phenomenon would be to add to maltol a smallquantity of a stronger chelating agent, in order to intercept possiblemetal ions before Maltol could do so. Thus, an examination of variouschelating agents in order to “protect” the Maltol from chelating metalions was done.

Procedure: To a 0.5% solution of 90% Maltol and 10% Polyquaternium-80 indemineralized water a chelating agent was added in concentrations of 25ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm and 250 ppm, then a chip ofstainless steel 316 (˜1×1 cm) was added to the solution for 12 hr.

The following chelating agents were tested: 1) DisodiumEDTA—Ethylenediaminetetraacetic acid disodium salt; 2)EDTMP—Ethylenediamine tetra (methylene phosphonic acid); 3) Alaninedi-acetic acid; 4) Ascorbic acid; 5) Sodium Gluconate; 6) Zincgluconate; 7) Vanillin; 8) Sodium vanillate; 9)Ethylenediamine-N,N-discuccinic acid trisodium salt (Natrlquest E30).

The absorbance at 410 nm was measured with spectrophotometer Genesys10uv (Thermo Scientific), the blank was a solution of 0.5% 90% Maltoland 10% Polyquaternium-80 in demineralized water.

The results with different chelators on stainless steel 316 aresummarized in Table 20 and FIG. 1.

TABLE 20 Concentration (%) Chelator 0.5 1 2 3 4 5 Disodium 0.022 0.0090.004 0.002 0 0 EDTA Beta Alanine 0.133 0.039 0.045 0.124 0.067 0.098diAcetic acid Sodium 0.022 0.04 0.042 0.045 0.005 0.006 gluconateAscorbic 0.182 0.162 0.145 0.155 0.101 0.06 acid Sodium 0.073 0.0440.386 0.226 0.078 0.12 vanillate Zinc 0.231 0.136 0.207 0.096 0.1470.058 gluconate L- 0.113 0.391 0.393 0.102 0.311 0.096 MethionineVanillin 0.037 0.053 0.062 0.05 0.159 0.048

The results with disodium EDTA on stainless steel 304 are summarized inTable 21 and FIG. 2.

TABLE 21 Concentration (%) Chelator 0.5 1 2 3 4 5 Disodium 0.061 0.0100.026 0.007 0 0 EDTA

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

1. A composition comprising a pyrone and at least one cationicsurfactant in a ratio that ranges from 70:30 to 99:1 by weight,respectively.
 2. (canceled)
 3. The composition of claim 1, wherein saidpyrone is selected from the group consisting of maltol, ethyl maltol orany derivative thereof.
 4. A composition comprising a maltol and atleast two cationic surfactants.
 5. The composition of claim 1, whereinsaid cationic surfactant is selected from a tertiary ammonium compoundand a quaternary ammonium compound.
 6. (canceled)
 7. The composition ofclaim 1, wherein said at least one cationic surfactant is a mixture ofat least one tertiary ammonium compound and one quaternary ammoniumcompound.
 8. The composition of claim 1, wherein said at least onecationic surfactant is a mixture of at least two quaternary ammoniumcompounds.
 9. The composition of claim 4, wherein said at least twocationic surfactants is selected from (i) a mixture of at least onetertiary ammonium compound and one quaternary ammonium compound; (ii) amixture of at least two quaternary ammonium compounds.
 10. (canceled)11. The composition claim 1, wherein said at least one quaternaryammonium compound is a monomeric compound.
 12. The composition of claim1, wherein said at least one quaternary ammonium compound is a polymericcompound.
 13. The composition of claim 1, wherein the ratio between saidquaternary ammonium salts ranges from 10:1 to 1:10.
 14. The compositionof claim 1, wherein said at least two cationic surfactants are in aratio of 1:0.1 to 0.1:1 by weight, respectively.
 15. The composition ofclaim 1, wherein said at least one quaternary ammonium is,independently, selected from the group consisting of:benzyldimethyldodecylammonium chloride, didecyldimethylammoniumchloride, dodecyltrimethylammonium chloride, hexadecyltrimethylammoniumchloride, Polyquaternium-2, Polyquaternium-80, Polyquaternium-11,Polyquaternium-52, Polyquaternium-17, Sodium Cocamidopropyl PG-DimoniumChloride Phosphate (Cola Lipid C), Laurdimoniumhydroxypropyldecylglucoside chloride (SugaQuat L-1010), Berberine, Berberrubine,Berberis vulgaris root extract, Isopropylbenzyl butylnorberberineiodide, Palmatine, Jatrorrhizine, Coptisine, Ungeremine, Epiberberine,Pseudoberberine, Stepharanine, Sinapine, or any combination thereof. 16.The composition of claim 1, in the form of a powder or a solution. 17.(canceled)
 18. (canceled)
 19. The composition of claim 1, being anantimicrobial formulation.
 20. The composition of claim 1, furthercomprising a chelating agent, or a salt thereof.
 21. (canceled)
 22. Thecomposition of claim 20, wherein said chelating agent is selected fromthe group consisting of: Disodium EDTA—Ethylenediaminetetraacetic aciddisodium salt, EDTMP—Ethylenediamine tetra (methylene phosphonic acid),Alanine di-acetic acid, Ascorbic acid, Sodium Gluconate, Zinc gluconate,Vanillin, Ethylenediamine-N,N-discuccinic acid trisodium salt(Natrlquest E30), pentetic acid (DTPA), and any combination thereof. 23.(canceled)
 24. An article comprising the composition claim
 1. 25.(canceled)
 26. The article of claim 24, being selected from the groupconsisting of: a personal care product, a fabric, a bandage, a wipe, apledget, a swab, a suppository, a dressing, a solution, a mousse, a pad,a patch, and a formulation in the form selected from the groupconsisting of: liquid, paste, cream, lotion, foam, gel, emulsion, anointment, and soap.
 27. (canceled)
 28. (canceled)
 29. A method ofinhibiting or reducing the formation of load of a microorganism inand/or on an article, the method comprising contacting said article withthe composition of claim 1, optionally wherein said microorganism isselected from bacteria, molds and fungi.
 30. (canceled)
 31. The methodof claim 29, wherein any one of: (i) said bacteria are Gram-positivebacteria selected from the group consisting of: Staphylococcus aureus,Bacillus cereus and Staphylococcus epidermidis or Gram-negative bacteriaselected from the group consisting of: Escherichia coli and Pseudomonasaeuruginosa; (ii) said fungi are Candida albicans: (iii) said mold isAspergillus niger.
 32. (canceled)
 33. (canceled)
 34. (canceled)